Oxygen Consumption In Vivo by Ultra-High Dose Rate Electron Irradiation Depends Upon Baseline Tissue Oxygenation.

Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship.

Methods And Materials: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator.

Rethinking the Role of Biodosimetry to Assess Risks for Acute Radiation Syndrome in Very Large Radiation Events: Reconsidering Legacy Concepts.

The development of effective uses of biodosimetry in large-scale events has been hampered by residual, i.e., "legacy" thinking based on strategies that scale up from biodosimetry in small accidents.

Re-examining What the Results of "a Measurement of Oxygen Level in Tissues" Really Mean.

Within this special issue, many eminent investigators report on measurements of oxygen (O) levels in tissues. Given the complexities of spatial and temporal heterogeneities of O in tissues and its many sources, this commentary draws attention to what such measurements do and do not actually assess regarding O levels in tissues. Given this limitation, it also discusses how these results can be used most effectively.

A Critical Analysis of Possible Mechanisms for the Oxygen Effect in Radiation Therapy with FLASH.

The aim of this review is to stimulate readers to undertake appropriate investigations of the mechanism for a possible oxygen effect in FLASH. FLASH is a method of delivery of radiation that empirically, in animal models, appears to decrease the impact of radiation on normal tissues while retaining full effect on tumors. This has the potential for achieving a significantly increased effectiveness of radiation therapy.

EPR biodosimetry: challenges and opportunities.

This paper briefly examines electron paramagnetic resonance (EPR) techniques to measure dose from exposure to external radiation, assessing their current status, potential future uses and the challenges impacting their progress. We conclude the uses and potential value of different EPR techniques depend on the number of victims and whether they characterize short- or long-term risks from exposure. For large populations, EPR biodosimetry based on in vivo measurements or using co-located inanimate objects offer the greatest promise for assessing acute, life-threatening risk and the magnitude and extent of such risk.

Implications of "flash" radiotherapy for biodosimetry.

Extremely high dose rate radiation delivery (FLASH) for cancer treatment has been shown to produce less damage to normal tissues while having the same radiotoxic effect on tumor tissue (referred to as the FLASH effect). Research on the FLASH effect has two very pertinent implications for the field of biodosimetry: (1) FLASH is a good model to simulate delivery of prompt radiation from the initial moments after detonating a nuclear weapon and (2) the FLASH effect elucidates how dose rate impacts the biological mechanisms that underlie most types of biological biodosimetry. The impact of dose rate will likely differ for different types of biodosimetry, depending on the specific underlying mechanisms.

Comparison of Tumor Control and Skin Damage in a Mouse Model after Ultra-High Dose Rate Irradiation and Conventional Irradiation.

Recent studies suggest ultra-high dose rate radiation treatment (UHDR-RT) reduces normal tissue damage compared to conventional radiation treatment (CONV-RT) at the same dose. In this study, we compared first, the kinetics and degree of skin damage in wild-type C57BL/6 mice, and second, tumor treatment efficacy in GL261 and B16F10 dermal tumor models, at the same UHDR-RT and CONV-RT doses. Flank skin of wild-type mice received UHDR-RT or CONV-RT at 25 Gy and 30 Gy.

Mean dose rate in ultra-high dose rate electron irradiation is a significant predictor for Oconsumption and HOyield.

. The objective of this study was to investigate the impact of mean and instantaneous dose rates on the production of reactive oxygen species (ROS) during ultra-high dose rate (UHDR) radiotherapy. The study aimed to determine whether either dose rate type plays a role in driving the FLASH effect, a phenomenon where UHDR radiotherapy reduces damage to normal tissues while maintaining tumor control.

A Radiation Biological Analysis of the Oxygen Effect as a Possible Mechanism in FLASH.

The delivery of radiation at an ultra-high dose rate (FLASH) is an important new approach to radiotherapy (RT) that appears to be able to improve the therapeutic ratio by diminishing damage to normal tissues. While the mechanisms by which FLASH improves outcomes have not been established, a role involving molecular oxygen (O) is frequently mentioned. In order to effectively determine if the protective effect of FLASH RT occurs via a differential direct depletion of O (compared to conventional radiation), it is essential to consider the known role of O in modifying the response of cells and tissues to ionising radiation (known as 'the oxygen effect').

Partial Oxygen Pressure Assessment in Subcutaneous and Intraperitoneal Sites Using Imaging of Solid Oxygen Probe.

The purpose of this study was to assess the natural partial oxygen pressure (pO) of subcutaneous (SC) and intraperitoneal (IP) sites in mice to determine their relative suitability as sites for placement of implants. The pO measurements were performed using oxygen imaging of solid probes using lithium phthalocyanine (LiPc) as the oxygen sensitive material. LiPc is a water-insoluble crystalline probe whose spin-lattice and spin-spin relaxation rates ( and ) are sensitive to the local oxygen concentration.

Evaluation of a Refined Implantable Resonator for Deep-Tissue EPR Oximetry in the Clinic.

Objectives: (1) Summarize revisions made to the implantable resonator (IR) design and results of testing to characterize biocompatibility;(2) Demonstrate safety of implantation and feasibility of deep tissue oxygenation measurement using electron paramagnetic resonance (EPR) oximetry.

Study Design: In vitro testing of the revised IR and in vivo implantation in rabbit brain and leg tissues.

Methods: Revised IRs were fabricated with 1-4 OxyChips with a thin wire encapsulated with two biocompatible coatings.

First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip.

Objective: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the 'OxyChip', as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing.

Methods: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery.

Measurement of Tissue Oxygen as a Novel Approach to Optimizing Red Blood Cell Quality Assessment.

The effectiveness of blood transfusions can be impacted by storage and extensive processing techniques that involve treatment of red blood cells (RBCs) with pathogen reduction technologies (e.g., UV-light and chemical treatment), ex vivo stem cell derivation/maturation methods, and bioengineering of RBCs using nanotechnology.

What Is the Meaning of an Oxygen Measurement? : Analysis of Methods Purporting to Measure Oxygen in Targeted Tissues.

Clinical measurements of O in tissues will inevitably provide data that are at best aggregated and will not reflect the inherent heterogeneity of O in tissues over space and time. Additionally, the nature of all existing techniques to measure O results in complex sampling of the volume that is sensed by the technique. By recognizing these potential limitations of the measures, one can focus on the very important and useful information that can be obtained from these techniques, especially data about factors that can change levels of O and then exploit these changes diagnostically and therapeutically.

Quantification of Oxygen Depletion During FLASH Irradiation In Vitro and In Vivo.

Purpose: Delivery of radiation at ultrahigh dose rates (UHDRs), known as FLASH, has recently been shown to preferentially spare normal tissues from radiation damage compared with tumor tissues. However, the underlying mechanism of this phenomenon remains unknown, with one of the most widely considered hypotheses being that the effect is related to substantial oxygen depletion upon FLASH, thereby altering the radiochemical damage during irradiation, leading to different radiation responses of normal and tumor cells. Testing of this hypothesis would be advanced by direct measurement of tissue oxygen in vivo during and after FLASH irradiation.

The impact of particulate electron paramagnetic resonance oxygen sensors on fluorodeoxyglucose imaging characteristics detected via positron emission tomography.

During a first-in-humans clinical trial investigating electron paramagnetic resonance tumor oximetry, a patient injected with the particulate oxygen sensor Printex ink was found to have unexpected fluorodeoxyglucose (FDG) uptake in a dermal nodule via positron emission tomography (PET). This nodule co-localized with the Printex ink injection; biopsy of the area, due to concern for malignancy, revealed findings consistent with ink and an associated inflammatory reaction. Investigations were subsequently performed to assess the impact of oxygen sensors on FDG-PET/CT imaging.

OxyChip Implantation and Subsequent Electron Paramagnetic Resonance Oximetry in Human Tumors Is Safe and Feasible: First Experience in 24 Patients.

Tumor hypoxia confers both a poor prognosis and increased resistance to oncologic therapies, and therefore, hypoxia modification with reliable oxygen profiling during anticancer treatment is desirable. The OxyChip is an implantable oxygen sensor that can detect tumor oxygen levels using electron paramagnetic resonance (EPR) oximetry. We report initial safety and feasibility outcomes after OxyChip implantation in a first-in-humans clinical trial (NCT02706197, www.

How best to interpret measures of levels of oxygen in tissues to make them effective clinical tools for care of patients with cancer and other oxygen-dependent pathologies.

It is well understood that the level of molecular oxygen (O ) in tissue is a very important factor impacting both physiology and pathological processes as well as responsiveness to some treatments. Data on O in tissue could be effectively utilized to enhance precision medicine. However, the nature of the data that can be obtained using existing clinically applicable techniques is often misunderstood, and this can confound the effective use of the information.

Dependence of Radiation-induced Signals on Geometry of Tooth Enamel Using a 1.15 GHz Electron Paramagnetic Resonance Spectrometer: Improvement of Dosimetric Accuracy.

We aim to improve the accuracy of electron paramagnetic resonance (EPR)-based in vivo tooth dosimetry using the relationship between tooth geometry and radiation-induced signals (RIS). A homebuilt EPR spectrometer at L-band frequency of 1.15 GHz originally designed for non-invasive and in vivo measurements of intact teeth was used to measure the RIS of extracted human teeth.